This project was recently initiated. Progress is primarily at the level of developing the necessary infrastructure to accomplish the project goals. As osteosarcoma is a rare cancer, obtaining suitable biospecimens is a major obstacle to studying this disease. To overcome this problem it has been necessary to reach outside of the intramural community. A collaboration to obtain specimens has been established with the Childrens Oncology Group (COG), the primary national cooperative clinical trials group for pediatric cancer, to sequence specimens collected under COG trial. As osteosarcoma had been selected by the TARGET project (NCIs Therapeutically Applicable Research to Generate Effective Treatments, http://target.cancer.gov/about/), the TARGET infrastructure has been used to facilitate the COG collaboration. This collaboration will provide samples for analysis. An additional aspect of the early phase of this project has been the development of the necessary sequencing infrastructure. Suitable sequencing and computational equipment has been installed to support this project, and the bioinformatics infrastructure for data analysis has also been developed. Data generation has begun on a panel of osteosarcoma cell lines. This will be highly useful for the long term goals of the project since well characterized cell lines can be used for functional investigation of the biologically important results obtained in the course of this research. We have now initiated the analysis of clinical biospecimens collected through the TARGET program.